Basket Clinical Trials: A New Era in Cancer Treatment

Anaheim, CA—Precision medicine continues to transform oncology, and it is not just the treatments that are changing; decades-old drug clinical trial designs have been remodeled to accommodate an evolving understanding of genetic drivers in cancer.

Historically, targeted therapy studies have been limited to 1 tumor type, said Dr Liu. If a patient tested positive for a mutation, he or she was randomized to a selective inhibitor or chemotherapy that is often ineffective. However, recent data confirm that genetic mutations are seldom limited to a single histology, although the implication for treatment remains unclear. He discussed an example of studies with crizotinib (Xalkori).

“We know that patients with ALK-positive non–small-cell lung cancer can benefit from crizotinib, but the ALK rearrangement is seen in other types of cancer, too,” said Dr Liu. “With this many cancers and genetic drivers, clinicians and drug developers need to study therapeutic agents based on genetic drivers, not histology,” he emphasized.

Vemurafenib Basket Study

In the past decade, umbrella studies, basket studies, and master/molecular allocation studies have been introduced to resolve these issues, said Dr Liu.

Vemurafenib (Zelboraf), an oral BRAF inhibitor with selectivity for the BRAF V600E mutation form of the kinase, is FDA approved for patients with unresectable or metastatic melanoma and the BRAF V600E mutation. In a recent basket study, however, vemurafenib was used in a variety of cancers with different primary disease sites and histologies, including lung cancer, cholangiocarcinoma, Erdheim-Chester disease and Langerhans-cell histiocytosis, anaplastic thyroid cancer, ovarian cancer, multiple myeloma, and colorectal cancer.

“The basket study yielded exciting discoveries,” said Dr Liu. “In the cohort of Erdheim-Chester disease and Langerhans-cell histiocytosis, for example, all patients enrolled in the study demonstrated fast and durable disease regression. In the past, these were considered orphan diseases without any treatment,” he said.

In another cohort, a singer who had not responded to multiple lines of previous therapy for glioblastoma had nearly a complete response to vemurafenib and was able to return to the stage after treatment.

“These results inspire us as investigators to bring this basket trial to our patients,” said Dr Liu. “Regardless of diagnosis, we’re seeing that it’s never a hopeless situation.”

“When the study moves to the next phase of development, we then have a better chance of keeping patients on the study so that their disease may benefit from the treatment,” explained Dr Liu.